In older adults, nocturnal sleep is often shallow and fragmented and this is associated with decreased alertness during the daytime. The timing of sleep is also modified, with earlier bedtimes and morning awakenings. Earlier timing and reduced amplitude have also been observed for a series of other 24-hour rhythms, including those of hormonal secretions and body temperature. These alterations are thought to reflect age-related changes in the central circadian rhythm system. In young adults, sleep is associated with increased release of growth hormone (GH) and elevated levels of peripheral melatonin concentrations. There is evidence to indicate that the nocturnal release of GH and melatonin contribute to the maintenance and quality of sleep. Thus, these rhythmicity. In older adults, the nocturnal release of both of these hormones is diminished by at least 50%. The overall purpose of this proposal is to test the hypothesis that age-related decreases in the nocturnal secretion of GH and melatonin contribute to diminished sleep duration and quality, diminished daytime alertness and to alterations in circadian rhythmicity. Two different procedures will be used in the proposed studies to restore the elevation of plasma GH levels at the beginning of sleep: 1. daily intravenous injection of Growth-Hormone-Releasing-Hormone (GHRH) at bedtime in a dosage calculated to produce a pulse of plasma GH levels similar to that observed in young adults; 2. daily oral administration of a non-toxic substance that enhances slow-wave (SW) sleep without suppressing REM sleep. Because SW sleep stimulates GH release, administration of this compound at bedtime is expected to result in an increase of GH release during the beginning of sleep. To restore a nocturnal profile of plasma melatonin levels similar to that observed in young adults, nocturnal melatonin secretion in elderly subjects will be enhanced by daily administration of melatonin via a transmucosal patch applied to the gum, in a dosage calculated to produce elevated nocturnal melatonin levels in the range observed in young adults. Each treatment will be compared to daily administration of a placebo. Each treatment condition will last 30 days. Similar numbers of older men and women will be studied. Each subject will be studied on three separate occasions: one week before the beginning of treatment, at the end of the first week of treatment and at the end of treatment. Each study will involve two consecutive days of continuous temperature recording with hourly tests of alertness and performance during the daytime and polygraphic sleep recording during the nighttime. On the second day, blood samples will be taken at 20-min intervals for the measurement of the 24-hour profiles of GH, melatonin, cortisol and TSH. In addition, glucose, insulin and C-peptide, will be measured to monitor possible metabolic effects and to examine possible alterations in the 24-hour pattern of glucose tolerance. Power spectral analysis will provide an accurate estimation of the timing and intensity of SW sleep.